The full content of Annals is available to subscribers

Copyright in the material you requested is held by American College Of Physicians
(unless otherwise noted). This email ability is provided as a courtesy, and by using
it you agree that that you are requesting the material solely for personal, non-commercial
use, and that it is subject to ACP's Conditions of Use.
The information provided in order to email this topic will not be used to send unsolicited
email, nor will it be furnished to third parties. Please refer to
American College Of Physicians'sPrivacy
Policy for further information.

From Queen's University, Kingston, Ontario, Canada; Institute for Clinical Evaluative Sciences and University of Toronto, Toronto, Ontario, Canada; Harvard Medical School and Harvard School of Public Health, Boston, Massachusetts; University of British Columbia, Vancouver, British Columbia, Canada; and Meyers Primary Care Institute of the University of Massachusetts Medical School, Fallon Clinic Foundation, and Fallon Community Health Plan, Worcester, Massachusetts.

Grant Support: By a Canadian Institutes for Health Research operating grant (no. 53124) and a Chronic Disease New Emerging Team program grant (no. 54010). The New Emerging Team program receives joint sponsorship from the Canadian Diabetes Association, the Kidney Foundation of Canada, the Heart and Stroke Foundation of Canada and the Canadian Institutes for Health Research Institutes of Nutrition, Metabolism & Diabetes and Circulatory & Respiratory Health. Dr. Gill is supported by an Ontario Ministry of Health and Long-Term Care Career Scientist Award. Dr. Bronskill is supported by a New Investigator Award through the New Emerging Team program. Dr. Anderson is supported by a Chair in Health Management Strategies from the University of Toronto. Dr. Rochon is supported by a Canadian Institutes for Health Research Investigator Award. Dr. Lee is supported by a fellowship grant from Eli Lilly.

Our study provides further evidence that use of atypical antipsychotics is associated with a small but significant increase in mortality among older adults with dementia. In addition, the risk for death associated with antipsychotics is apparent after as little as 1 month of use and may persist for 6 months. Finally, these data provide independent confirmation of reports that use of conventional antipsychotics confers an even greater risk for death than does use of atypical antipsychotics (15, 18).

Comments

Please read the other comments before posting. Contributors must reveal any conflict
of interest.
Comments are moderated and will appear on the site at the discretion of The American
College of Physicians editorial staff. Please be sure your email address is
updated in your account, otherwise the American College of Physicians will not be
able to contact you about your comment.

* = Required Field

Comment Author(s)* (if multiple authors,
separate names by comma)

Example: John Doe

Affiliation & Institution*

Disclosure of Any Conflicts of Interest*
(applies to the past 5 years and foreseeable future) Indicate any potential conflicts
of interest of each author below, including specific financial interests and relationships
and affiliations relevant to the subject matter or materials discussed in the manuscript
(eg, employment/affiliation, grants or funding, consultancies, honoraria, speakers
bureau, stock ownership or options, expert testimony, royalties, donation of medical
equipment, or patents filed, received, or pending). If all authors have none, check
"No potential conflicts or relevant financial interests" in the box below. Please
also indicate any funding received in support of this work. The information will
be posted with your response.

This article reinforces the point that one should always attempt non- pharmacological methods of managing challenging behaviour in those with dementia. However, I was not entirely sure if like was being compared with like in the comparison of mortality between those given antipsychotic drugs and those not. Was the incidence and nature of challenging behaviour the same in both groups? Behavioural disturbance may be a feature of more advanced dementia. It may also worsen in the presence of other pathology - so difficult to identify in this group of patients. Might the higher incidence in mortality be expalined by a greater incidence of unidentified intercurrent patholgy causing diturbed behaviour, rather than a reaction to the drugs themselves?

Confounding Factor

Posted on
June 6, 2007

Thomans A. Barley

No Affiliation

Conflict of Interest:
None Declared

The confounding factor not addressed by the antipsychotic drug use review article is who is being treated and why. I do not give antipsychotics to patients doing well. They are reserved for those having the most problems. They are the highest risk group for falls, poor eating, an inability to care for their physical needs, refusing their meds, etc. I use typical antipsychotics only in patients I consider terminally ill due to the long term side effects. Until you treat a large group of patients with antipsychotics who don't need them you cannot prove harm or increased mortality. I know they relieve frightful distress and allow safety of the staff and facility to be enhanced. Thomas Barley MD

Conflict of Interest:

None declared

This could be due to lower DHEA levels...

Posted on
June 10, 2007

James M. Howard

independent

Conflict of Interest:
None Declared

I suggest these findings may be explained by reductions in DHEA caused by antipsychotic medications in individuals whose DHEA already is low.

A case may be made that dementia is due to low DHEA. DHEA naturally declines in old age and is probably lower in individuals exhibiting dementia.

A case may be made that antipsychotic medication reduces DHEA. The effect of reducing DHEA is to reduce activity in lower parts of the brain that are active without executive, or upper level, control. Reducing DHEA reduces lower brain activity and makes the treated individual more manageable.

Antipsychotic medications, old and new, increase prolactin. Prolactin specifically and directly stimulates the production of DHEA. I suggest high prolactin indicates that DHEA is not being produced, thereby reducing DHEA feedback of prolactin production. Increased prolactin levels caused by antipsychotic medications may indicate that DHEA is being reduced, therefore, reducing lower brain activity.

Low DHEA of dementia and in older individuals, who are in the natural decline of DHEA, are vulnerable to further low DHEA levels which may result in death. I suggest lowering DHEA in these individuals via antipsychotic medications may explain the findings of Gill, et al.

Conflict of Interest:

None declared

Antipsychotic use and mortality rate in dementia

Posted on
July 4, 2007

Abid Iraqi

Syracuse VA Medical Center, Syracuse, NY

Conflict of Interest:
None Declared

To The Editor:

Gill and colleagues (1) highlight the substantial difference in the mortality rate of dementia patients who took antipsychotics as compared to those who did not take antipsychotics. However, it does not seem that their study took into consideration as to how long these patients had dementia. Dementia has shown to shorten life expectancy. In the earlier studies, estimates of median survival from the onset of symptoms vary from 5 years (range, 1 to 13) (2) to 9.3 years (range, 1.8 to 16 or more) (3), and the later study showed unadjusted overall median survival of 6.60 years, with an adjusted median survival of 3.33 years after the onset of dementia (4). If patients in antipsychotic group had dementia for a longer duration then they were anticipated to have a shorter life expectancy to begin with. Additionally, initiation and/or use of antipsychotic use in dementia patients may have been an indication that their dementia was getting worse as usually incidence of behavioral disturbances increases with the advancement in the stages of dementia. Is it possible that due to progression in dementia, their life expectancy was shorter and was not necessarily due to antipsychotic use?.

We agree that antipsychotics should be used cautiously and perhaps may be used, as mandated in the OBRA regulations of 1987, as a last resort and not as the first option.

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College
of Physicians (ACP). All text, graphics, trademarks, and other intellectual property
incorporated into the slide sets remain the sole and exclusive property of the ACP.
The slide sets may be used only by the person who downloads or purchases them and
only for the purpose of presenting them during not-for-profit educational activities.
Users may incorporate the entire slide set or selected individual slides into their
own teaching presentations but may not alter the content of the slides in any way
or remove the ACP copyright notice. Users may make print copies for use as hand-outs
for the audience the user is personally addressing but may not otherwise reproduce
or distribute the slides by any means or media, including but not limited to sending
them as e-mail attachments, posting them on Internet or Intranet sites, publishing
them in meeting proceedings, or making them available for sale or distribution in
any unauthorized form, without the express written permission of the ACP. Unauthorized
use of the In the Clinic slide sets will constitute copyright infringement.